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Administrative data

Description of key information

The median lethal dose (LD50) of FAT 40865/A TE after single oral administration to female rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-07-2014 TO 24-10-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
None
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Animal Breeding
RCC Laboratories India Private Limited
Genome Valley, Turkapally
Shameerpet (Mandal)
Ranga Reddy District
Hyderabad – 500 078
India

- Age at study initiation:9 - 11 weeks
- Weight at study initiation:Females: 140.2 to 178.3 g
- Fasting period before study:17 Hours
- Housing:Housed in groups of three animals each in Polycarbonate cages (approximate internal dimensions of 365 mm x 202 mm x 180 mm height) with paddy husk bedding. Results of analyses for contaminants will be archived at RCC Laboratories India Private Limited.
- Diet (e.g. ad libitum):Nutrilab rodent feed from Provimi Animal Nutrition India Pvt. Ltd., (Batch No. 0001887772 and 0001946849) was provided ad libitum. Results of analyses for contaminants will be archived at RCC Laboratories India Private Limited
- Water (e.g. ad libitum):Aquaguard filtered tap water was provided ad libitum. Results of bacteriological, chemical and contaminant analyses will be archived at RCC Laboratories India Private Limited.
- Acclimation period:Under laboratory conditions for 8 days for Step I, Step III and 13 days for Step II and Step IV animals, after veterinary examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONSStandard Laboratory Conditions
- Temperature (°C):21.9 to 23.7o C
- Humidity (%):61 to 70%
- Air changes (per hr):adequate (above 10) air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours light and 12 hours dark.

IN-LIFE DATES: From: July 31st 2014 To: September 9th 2014
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30mg/ml and 200mg/ml
- Amount of vehicle (if gavage): 10ml
- Justification for choice of vehicle: Universal Solvent
MAXIMUM DOSE VOLUME APPLIED: 10ml/Kg


- Rationale for the selection of the starting dose: Since no information on the toxicity available, the starting dose is selected as 300 mg/kg body weight. The test procedure was followed the attached scheme described in Annex 2c, OECD Guideline 423, adopted 17th December 2001
Doses:
Step I 300 mg/kg
Step II 300 mg/kg
Step III 2000 mg/kg
Step IV 2000 mg/kg
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration:
14 days
- Frequency of observations and weighing:
Mortality / Viability
Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0 (in common with the clinical signs) and twice daily during days 1-14 (once on day of sacrifice).
Body weights
On test days 0 (prior to dose administration), day 7, and 14.
Clinical signs
Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0. Once daily during days 1-14.

- Necropsy of survivors performed:
yes


GROUPS / STEPS Dose
( mg/kg) NUMBER OF ANIMALS
PER STEP
(Female) ANIMAL NUMBER
First Step 300 3 01 - 03
Second Step 300 3 04 - 06
Third Step 2000 3 07 - 09
Fourth Step 2000 3 10 - 12

Statistics:
No statistical analysis was done
Preliminary study:
No
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Step I 3 females treated at 300 mg/kg Mortality ‘0 out of 3’
Step II 3 females treated at 300 mg/kg Mortality ‘0 out of 3’
Step III 3 females treated at 2000 mg/kg Mortality ‘0 out of 3’
Step IV 3 females treated at 2000 mg/kg Mortality ‘0 out of 3’
Clinical signs:
All the animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) treated at 300 mg/kg body weight appeared normal at first 30 minutes, 1, 2 , 3 and 4 hour observation on day 0 after treatment and throughout the experiment period ( up to day 14).
All the animals of Step III (Animal No. 07, 08 and 09) and Step IV (Animal No. 10, 11 and 12) treated at 2000 mg/kg body weight showed dullness at first 30 minutes, 1, 2, 3 and 4 hour observation on day 0 after treatment and appeared normal from day 1 of observation period to the last day of observation period (day 14)
Body weight:
All the animals gained body weight by days 7 and 14 as compared to day 0
Gross pathology:
No abnormalities were observed in any of the treated animals at terminal sacrifice

None

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on the results, the median lethal dose (LD50) of FAT 40865/A TE after single oral administration to female rats, observed over a period of 14 days was greater than 2000 mg/kg body weight.
Executive summary:

An OECD 423 guideline study was performed in accordance to GLP to assess the oral toxicity of test item FAT 40865/A over a period of 14 days. The test item FAT 40865/A TE was administered to Wistar rats by oral gavage at a dose level of 300 mg/kg body weight and 2000 mg/kg body weight to 2 dose groups in 4 steps. The former two steps (Step I & II) represents the dose group of 300 mg/kg body weight and later two steps (Step III & IV) represents the dose group of 2000 mg/kg body weight. Three animals were allocated to each step. The test item was formulated in vehicle (distilled water) at a concentration of 30 mg/mL for Step I and Step II and 200 mg/mL for Step III and Step IV, administered at a dose volume of 10 mL/kg body weight.

The animals were observed daily during the acclimatization period and, mortality/viability, and clinical signs were recorded. All the animals were observed for clinical signs during first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0 and once daily during test days 1‑14. Mortality/viability was recorded during first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0 (in common with the clinical signs) and twice daily during days 1-14 (once on day of sacrifice). Body weights were re­corded on test day 0 (prior to administration), and on day 7 and 14. All the animals were necropsied and examined macroscopically at the end of observation period.

All the animals appeared normal throughout the acclimatization period.

The animals were treated as follows:

Step I           3 females treated at 300 mg/kg        Mortality ‘0 out of 3’

Step II          3 females treated at 300 mg/kg        Mortality ‘0 out of 3’

Step III         3 females treated at 2000 mg/kg      Mortality ‘0 out of 3’

Step IV        3 females treated at 2000 mg/kg      Mortality ‘0 out of 3’

All the animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) treated at 300 mg/kg body weight appeared normal at first 30 minutes, 1, 2 , 3 and 4 hour observation on day 0 after treatment and throughout the experiment period ( up to day 14).

All the animals of Step III (Animal No. 07, 08 and 09) and Step IV (Animal No. 10, 11 and 12) treated at 2000 mg/kg body weight showed dullness at first 30 minutes, 1, 2, 3 and 4 hour observation on day 0 after treatment and appeared normal from day 1 of observation period to the last day of observation period (day 14).

All the survived animals gained body weight by days 7 and 14 as compared to day 0.

No abnormalities were observed in any of the treated animals at terminal sacrifice.

Based on the results, the median lethal dose (LD50) of FAT 40865/A TE after single oral administration to female rats, observed over a period of 14 days was greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
High quality study conducted in compliance with GLP

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

An OECD 423 guideline study was performed in accordance to GLP to assess the oral toxicity of test item FAT 40865/A over a period of 14 days. The test item FAT 40865/A TE was administered to Wistar rats by oral gavage at a dose level of 300 mg/kg body weight and 2000 mg/kg body weight to 2 dose groups in 4 steps. The former two steps (Step I & II) represents the dose group of 300 mg/kg body weight and later two steps (Step III & IV) represents the dose group of 2000 mg/kg body weight. Three animals were allocated to each step. The test item was formulated in vehicle (distilled water) at a concentration of 30 mg/mL for Step I and Step II and 200 mg/mL for Step III and Step IV, administered at a dose volume of 10 mL/kg body weight.

No mortality was observed at any step. All the survived animals gained body weight by days 7 and 14 as compared to day 0. No abnormalities were observed in any of the treated animals at terminal sacrifice. Hence, based on the findings of the study, the median lethal dose (LD50) of FAT 40865/A TE after single oral administration to female rats, observed over a period of 14 days was greater than 2000 mg/kg body weight.

Acute inhalation toxicity:

Currently no study to assess acute inhalation toxicity is available. But due to the intrinsic properties of the test item (low volatility as the vapour presseure is 7.28*10-3Pa and high water solubility of 17.76 g/L, indicating if vapours are produced will be trapped in the mucus) and the high values of the acute oral toxicity studies (LD50 >2000 mg/kg bw), indicate no adverse effects are expected via the inhalation route. Experience with similar chemical structures demonstrated that it is very unlikely that toxicity related to intrinsic properties of the test item only show up via the inhalation route and not via the oral-gastric route of exposure.

Acute dermal toxicity:

Currently no study to assess acute dose dermal toxicity is available.

However, as per the section 8.5.3 of Regulation (EC) 1906/200, testing by the dermal route does not need to be conducted if: i) the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and ii) no systemic effects have been observed inin vivostudies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of anin vivostudy by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies).

For this substance, in a local lymph node assay with mice, three groups, each of four animals, were treated with 50 µL (25 µL per ear) of the test item as a solution in dimethyl formamide at concentrations of 2%, 5% or 10% w/w, for three consecutive days. No clinical signs, systemic toxicity or mortality was observed.

Similarly, the substance does not meetthe criteria for classification as acute toxicity or STOT SE by the oral route (LD50 of >2000 mg/kg bw). Hence, the dermal study was not conducted.

Justification for classification or non-classification

Based on the results of an acute oral toxicity study, FAT 40865 does not require classification for acute toxicity as per the CLP (Regulation 1272/2008) criteria.